Velocity-selective (VS) pulse trains can provide unique functionalities when designing pulse sequences for various Magnetic Resonance Imaging (MRI) based hemodynamic evaluation: MR angiography (MRA); blood flow (perfusion), blood volume, or transit time; oxygen extraction fraction; metabolic rate of oxygen.
Quantitative measurement of cerebral blood volume (CBV), in addition to cerebral blood flow (CBF), provides more thorough examination of cerebral circulation for both neurophysiology and brain disorders. Baseline CBV is indispensable for understanding BOLD signal mechanism with various biophysical models and CBV change during activation also provides important fMRI contrast. The ratio of CBV to CBF, called mean transit time (MTT), is another important hemodynamic parameter which reflects the local cerebral perfusion pressure in ischemic episodes. For patients with occluded carotid arteries, increased oxygenation extraction fraction (OEF) and CBV yet at normal CBF (autoregulatory vasodilation) were associated with higher risk of stroke. For patients with cerebral gliomas, new blood vessel formation (angiogenesis) and thus elevated CBV indicated higher tumor grading with poor prognosis.
Regional CBV values have been imaged in the clinic on different modalities: positron emission tomography (PET) with inhaled C15O, single photon emission computed tomography (SPECT) using radioisotopes such as 99mTc, dynamic perfusion computer tomography (PCT) using iodinated tracers, and dynamic susceptibility contrast (DSC)-MRI with injected Gadolinium (Gd)-based contrast agents. Being free of ionizing radiation, DSC-MRI obtains perfusion-weighted signal during the first pass of the contrast bolus through the vasculature. In the clinical applications, DSC-MRI often reports qualitative perfusion measures, such as relative CBV compared to a normal white mater area. For absolute quantification of CBV, this technique faces several challenges, e.g., identification of global arterial input function (AIF) from a pure blood voxel, consideration of the delay and dispersion of the local AIF, and non-linear response of intravascular Gd concentration. A newer Gd-based approach applies an inversion recover pulse sequence with the blood signal nulled before the bolus administration and fully recovered after the contrast passage due to the shortening of blood T1, hence generating the normalized pre/postcontrast difference images as absolute CBV maps. However, the risks of developing nephrogenic systemic fibrosis (NSF) limit Gd-enhanced MRI techniques on patient population with impaired renal function and the finding of gadolinium deposition in neuro tissues even for people without kidney diseases warrant caution of repeat use of certain Gd-based contrast agents. Iron oxide nanoparticle was used instead in another steady-state study which calculated relative CBV maps through subtraction of pre/post contrast.
To lower safety risks and cost, it is long desired to have noninvasive MRI methods for perfusion measurement without requiring any exogenous contrast agent. Arterial spin labeling (ASL) methods acquire perfusion-weighted signal by subtracting the supplying arterial blood-labeled images from the controlled pairs. Although becoming more standardized for clinical applications, ASL mainly provides CBF measurement. Spatially-selective ASL techniques were developed to estimate the volume of the arterial blood compartment, CBVa.
Intravoxel incoherent motion (IVIM) technique applies motion-sensitized gradients with multiple b values and extracts information of both the fraction of blood compartment and diffusion constants of tissue and microvasculature by fitting a bi-exponential model. IVIM assumes that water spins flowing in the capillaries change velocity and direction several times during the applied gradient waveforms, much like a random walk of spins in the diffusion process, except about 10 times faster. Despite gaining popularity in clinical studies for different organs, the quantification precision and accuracy of this fitting-based method still suffers methodological issues such as requirement of high signal-to-noise ratio (SNR) and the validity of the bi-exponential model, especially in the brain where CBV is smaller than 5% and pulsatile flow of cerebrospinal fluid (CSF) is present. A further overlooked drawback of the IVIM signal model is its neglecting of the T1 and T2 relaxation factors in each compartment, thus the results are dependent on the employed repetition time (TR) and echo time (TE) respectively.
It would therefore be advantageous to provide a reliable method for measurement of blood volume without having to inject exogenous contrast.